The Relation between Hamstring Strain Injury and Physical Characteristics of Japanese Collegiate Sepak Takraw Players.

The aim of this study was to investigate the injuries in Japanese collegiate sepak takraw players. We primarily focused on hamstring strain injury (HSI), and investigated the associated physical characteristics. The study included 77 Japanese collegiate sepak takraw players who were interviewed; data were collected regarding injuries sustained by them during the game within the past year. The hip range of motion (ROM) was measured. The total number of injuries was 48 in a year. The rate of HSI was the highest (31.3%) among all the injuries. All HSIs occurred in the dominant leg because of the sunback spike. Using the Mann-Whitney U test, significant differences in age and sport-related experience were observed between the injured group and uninjured group. Upon using logistic regression analysis, the presence of a HSI was found to be associated with the sport-related experience (adjusted odds ratio [OR], 0.30; 95% confidence interval [CI], 0.12-0.77) and the hip extension ROM (adjusted OR, 0.81; 95% CI, 0.66-0.99) after adjusting for sex, sport-related experience, and the hip ROM. HSI is the most common injury in Japanese collegiate sepak takraw players. Short sport-related experience and small hip extension ROM are related with the occurrence of HSI.

Biological clock dysfunction exacerbates contact hypersensitivity in mice.

BACKGROUND: Immediate-type skin allergic reactions, such as passive cutaneous anaphylactic reaction, are associated with circadian rhythm, but the role of circadian mechanisms on delayed-type skin allergic reactions, such as contact hypersensitivity (CHS), remains uncertain. In mice, CHS, a T-cell-mediated immune response, is a classic model of human allergic contact dermatitis. OBJECTIVES: We investigated whether biological clock dysfunction affects CHS pathogenesis in CLOCK mutant mice compared with wild-type (WT) mice. METHODS: Mice were treated with 2,4,6-trinitro-1-chlorobenzene (TNCB) on the abdominal skin on day 0 (sensitization) and then treated with TNCB on the ears on day 5 (challenge). RESULTS: We found that biological clock dysfunction resulted in severe inflammation. Ear swelling, serum immunoglobulin E level and mast cell number were significantly increased in CLOCK mutant mice compared with WT mice. These results provide evidence that CLOCK mutation promotes the T-helper type 2 immune response and exacerbates CHS. Corticosterone has a protective effect on CHS. The serum corticosterone level lost rhythmicity and showed a decreased daily level in CLOCK mutant mice compared with WT mice, supporting the exacerbating effect of CLOCK mutation on CHS. Adrenalectomy markedly worsened TNCB-induced CHS in WT mice but not in CLOCK mutant mice. In addition, dramatic dexamethasone-induced protection of CHS was observed in CLOCK mutant mice compared with WT mice. CONCLUSIONS: The present results suggest that circadian rhythm might be an important factor in the regulation of CHS via corticosterone rhythmicity and/or level.

Relationship between buccal mucosa ridging and viscoelastic behaviour of oral mucosa.

The aim of this study was to clarify the relationship between the buccal mucosa ridging (BMR), which has been mentioned to be a clinical sign of clenching, and the viscoelastic behaviour of oral mucosa. Twenty-three people with BMR and 21 people without BMR participated as volunteers in this study. Measurements of viscoelastic behaviour were performed using a suction viscoelastic meter on central part of lower labial mucosa. A suction pressure of 300 hPa was applied for 2 s and then released for 2 s, and the time-dependent changes in the deformation of the mucosa over this 4 s were recorded as a deformation curve. Distensibility, remaining deformation and elastic recovery, which describe viscoelastic behaviour, were calculated by the deformation curve. These parameters were compared between groups with and without BMR. No significant difference was found in distensibility between the two groups (P=0·349). There were significant differences for the remaining deformation (P=0·012) and the elastic recovery (P=0·032), and the group with BMR showed higher remaining deformation and lower elastic recovery than the group without BMR. Based on these results, it clarified that the BMR is related to the mucosal viscoelastic behaviour, in particular remaining deformation and elastic recovery.

Influence of concentration of fragrances on salivary alpha-amylase.

The objective is to reveal the influence of the concentration of fragrances on salivary biomarkers, which reflect the human stress system, in 15 female young healthy adults. Lavandula officinalis and Citrus aurantium were used as the test samples. Salivary biomarkers such as alpha-amylase activity (AMY), cortisol (CORT) and dehydroepiandrosterone (DHEA) were measured during baseline, inhalation and post-inhalation periods. Our results indicated that (i) a significant difference was not observed for the control and the 3 wt% test samples, however, the AMY was decreased by inhalation of the 1 wt% test samples (P < 0.05); (ii) AMY levels changed more significantly than did the hormone levels; (iii) a tendency of negative correlation was not observed between DHEA and CORT. It was considered that the time-course change of AMY might be a useful index of the inhalation of fragrances, which reflects the acute psychosomatic reactivity of humans.

Calreticulin mutant mice develop essential thrombocythemia that is ameliorated by the JAK inhibitor ruxolitinib.

Mutations of calreticulin (CALR) are detected in 25-30% of patients with essential thrombocythemia (ET) or primary myelofibrosis and cause frameshifts that result in proteins with a novel C-terminal. We demonstrate that CALR mutations activated signal transducer and activator of transcription 5 (STAT5) in 293T cells in the presence of thrombopoietin receptor (MPL). Human megakaryocytic CMK11-5 cells and erythroleukemic F-36P-MPL cells with knocked-in CALR mutations showed increased growth and acquisition of cytokine-independent growth, respectively, accompanied by STAT5 phosphorylation. Transgenic mice expressing a human CALR mutation with a 52 bp deletion (CALRdel52-transgenic mice (TG)) developed ET, with an increase in platelet count, but not hemoglobin level or white blood cell count, in association with an increase in bone marrow (BM) mature megakaryocytes. CALRdel52 BM cells did not drive away wild-type (WT) BM cells in in vivo competitive serial transplantation assays, suggesting that the self-renewal capacity of CALRdel52 hematopoietic stem cells (HSCs) was comparable to that of WT HSCs. Therapy with the Janus kinase (JAK) inhibitor ruxolitinib ameliorated the thrombocytosis in TG mice and attenuated the increase in number of BM megakaryocytes and HSCs. Taken together, our study provides a model showing that the C-terminal of mutant CALR activated JAK-STAT signaling specifically downstream of MPL and may have a central role in CALR-induced myeloproliferative neoplasms.

Potentiation of anticancer agents by new synthetic isoprenoids. I. Inhibition of the growth of cultured mammalian cells.

In this study, 9 new synthetic isoprenoids with 9-10 isoprene chains were tested. One-fifth of the D10 value (concentration of drug that reduced colony-formation ability to 10% that of control) for each isoprenoid was calculated from dose-response curves of Chinese hamster V79 cells or human HeLa cells in culture. That dose was combined with various anticancer agent [1-(4-amino-2-methylpyrimidin-5-yl)methyl-3-(2-chloroethyl)-3-n itrosurea HCl, bleomycin A2 (BLM), cisplatin, doxorubicin (Dx), 5-fluorouracil, mitomycin, and 6-mercaptopurine] to test whether isoprenoids can potentiate the cytotoxic effect of anticancer agents against cultured mammalian cells. Among the 9 isoprenoids tested, decaprenoic acid, dacaprenylamine.HCl, and N-(p-methylbenzyl)decaprenylamine.HCl significantly potentiated BLM and Dx. Some isoprenoids increased intracellular levels of anticancer agents. Both enhanced uptake and reduced efflux of Dx were observed.

Potentiation of anticancer agents by new synthetic isoprenoids. II. Inhibition of the growth of transplantable murine tumors.

The antitumor effects of combinations of synthetic isoprenoids-decaprenylamine.HCl, N-(p-methylbenzyl)decaprenylamine.HCl [N-(PMB)-decaprenylamine.HCl], and decaprenoic acid-with anticancer agents were studied in male ICR mice with ascites sarcoma 180 (S180) and in male BALB/c mice with fibrosarcoma Meth A. Decaprenylamine.HCl, N-(PMB)-decaprenylamine.HCl, and decaprenoic acid were tested in combination with bleomycin A2 (BLM) on S180. Decaprenoic acid was also examined in combination with BLM or 5-fluorouracil (FUra) for effects on fibrosarcoma Meth A. The dosages of synthetic isoprenoids used in the combination therapy were much below the median lethal dose. In the low-dosage schedule, decaprenylamine.HCl, N-(PMB)-decaprenylamine.HCl or decaprenoic acid considerably enhanced the antitumor effect of BLM on S180; e.g., the T/C value (mean survival time of treated mice/mean survival time of controls) for decaprenylamineHCl plus BLM, N-(PMB)-decaprenylamine.HCl plus BLM, or decaprenoic acid plus BLM was 294, 357, and 279% respectively, and the combinations increased life-span 2.4-fold, 2.3-fold, or 1.8-fold, respectively, as compared to the effects of BLM alone. The combination of BLM or FUra with decaprenoic acid, when administered by iv injection to mice with fibrosarcoma Meth A (solid tumor system), did not produce synergism. However, a preventive effect of decaprenoic acid monotherapy was observed: Decaprenoic acid at 3 mg/kg resulted in 38.9% suppression of tumor growth 21 days after inoculation.

Transduction of antisense cyclin D1 using two-step gene transfer inhibits the growth of rat hepatoma cells.

Cyclin D1, one of the G(1) cyclins, is frequently overexpressed in several types of carcinomas and is thought to play an important role in tumorigenesis and tumor progression including hepatocellular carcinoma. We constructed a retrovirus vector-carrying rat cyclin D1 cDNA in the reverse orientation, resulting in expression of antisense (AS) cyclin D1 mRNA. For efficient transduction of this recombinant retrovirus, two-step gene transfer was performed. The rat hepatoma cell line (dRLh84) was infected with this recombinant retrovirus after preinfection with adenovirus expressing the retrovirus receptor. In the rat hepatoma cells, AS cyclin D1 mRNA was expressed, inducing a decrease in the expression of endogenous cyclin D1 mRNA and an inhibition of cell growth. Moreover, two-step gene transfer of AS cyclin D1 into s.c. hepatoma xenografts resulted in inhibition of tumor growth and prolonged animal survival. In the virus-infected tumor xenografts, expression of cyclin D1 was immunohistochemically inhibited, and apoptosis of hepatoma cells was detected. These findings suggest that transduction of AS cyclin D1 is useful as an adjunct to standard treatments for hepatocellular carcinoma.

The structure of the menaquinones with a tetrahydrogenated isoprenoid side-chain.

Menaquinones with a tetrahydrogenated isoprenoid side-chain of Oerskovia turbata and Brevibacterium lipolyticum were cyclized to the chromenyl acetate derivatives, which were then submitted to ozonolysis, followed by reduction with dimethylsulfide. The mass-spectrometric analyses of the ozonolysis products revealed the ion peaks at m/e 464 (M+), 449, 422, 407, 267 and 225. These results suggest that the two saturated double bonds are located continuously in the second and third units of the chain starting from the quinone ring, and the menaquinones are designated as 2-methyl-3-II,III-tetrahydromultiprenyl-1,4-naphthoquinone.

On the chemical structure of menaquinones with the tetrahydrogenated isoprenoid side chain.

New menaquinones have been isolated from Oerskovia turbata and Brevibacterium lipolyticum in the nocardioform and coryneform groups of bacteria, which have been identified to be a series of menaquinones with a tetrahydrogenated isoprenoid chain, designated as menaquinone-9(H4) and menaquinone-8(H4), respectively, by thin layer chromatography, ultraviolet and infrared spectrophotometry and mass spectrometry. The nuclear magnetic resonance spectra of the quinones have revealed that all the two saturated dolble bonds occur in the internal units of the isoprenoid side chain.

An ornithine-containing lipid isolated from Gluconobacter cerinus.

The three ornithine-containing lipids of Gluconobacter cerinus were isolated from each other. One of the three lipids was postulated as Nalpha-3-hydroxypalmitoylornithine, to the fatty acid moiety of which 2-hydroxy fatty acid is linked by an ester linkage. The 2-hydroxy acid was possibly cis-11, 12-methylene-2-hydroxyoctadecanoate. Such an ornithine-containing lipid was found to be distributed in other acetic acid bacteria.

Fusion of dioleoylphosphatidylcholine vesicles induced by an amphiphilic cationic peptide and oligophosphates at neutral pH.

Peptide E5 is an analogue of the fusion peptide of influenza virus hemagglutinin and K5 is a cationic peptide which has an arrangement of electric charges complementary to that of E5. We reported that a stoichiometric mixture of E5 and K5 caused fusion of large unilamellar vesicles (LUV) of neutral phospholipids (Murata, M., Kagiwada, S., Takahashi, S. and Ohnishi, S. (1991) J. Biol. Chem. 266, 14353-14358). K5 caused fusion of LUV composed of dioleoylphosphatidylcholine (DOPC) at pH > 10, but not at neutral pH. In the presence of oligophosphates, such as 1 mM ATP, GTP, or polyphosphate, K5 caused rapid and efficient fusion of DOPC LUV at neutral pH without hydrolysis of oligophosphate groups, but another anions such as citrate, acetate, AMP, phosphate, or EDTA were ineffective. The peptide/oligophosphate-induced fusion behaviors have been investigated by a fluorescence resonance energy transfer assay for lipid mixing of LUV and negative staining electron microscopy. At higher ionic strengths ( > 0.3 M KCl) or in the presence of 5.0 mM MgCl2, the fusion was inhibited. Even at the inhibitory conditions, the association of K5 with lipid vesicles at neutral pH was directly confirmed by the Ficoll gradient assay method and by blue shifts of the tryptophan fluorescence of the peptide. A nonhydrolyzable GTP analogue, GTP gamma S, also induced fusion. These observations suggested that the electrostatic interactions between the positive and negative charges of K5 and oligophosphate, respectively, induced complex formation, triggering membrane fusion.

Correlation between minimal secretory capacity of pancreatic beta-cells and stability of diabetic control.

The significance of the minimal secretory capacity of pancreatic beta-cells for the stability of the plasma glucose level was studied in 20 patients with insulin-dependent diabetes mellitus. Changes in plasma concentrations of major counterregulatory hormones in response to hypoglycemia were also investigated in these patients to clarify their contribution to diabetic brittleness. beta-Cell function was evaluated on the basis of elevation of plasma C-peptide immunoreactivity (CPR) during the intravenous glucagon test with a highly sensitive assay for plasma CPR that could detect as little as 0.03 ng/ml. After stimulation with glucagon, a significant increase in plasma CPR was observed in 10 of the patients whose beta-cell function had been evaluated as completely depleted by a conventional assay for plasma CPR. A clear inverse correlation was found between the secretory capacity of pancreatic beta-cells measured in this way and the degree of glycemic instability (r = -.74, P less than .01). Infusion of insulin at a rate of 0.15 U.kg-1.h-1 for 60 min caused a continuous decrease in the plasma glucose level, resulting in neuroglycopenia in 7 of the 10 CPR nonresponders but only 2 of the CPR responders. During insulin-induced hypoglycemia, plasma glucagon immunoreactivity did not increase in the CPR nonresponders but increased significantly in the CPR responders. A positive correlation was found between the minimal residual beta-cell capacity and the responsiveness of alpha-cells to hypoglycemia (r = .65, P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Kinetics of HbA1c, glycated albumin, and fructosamine and analysis of their weight functions against preceding plasma glucose level.

OBJECTIVE: To examine the kinetics of HbA1c, glycated albumin (GA), and fructosamine (FA) levels in response to plasma glucose change and their relationship with the preceding plasma glucose level. RESEARCH DESIGN AND METHODS: The time courses of HbA1c, GA, and FA after acute glycemic normalization were observed in nine patients with newly diagnosed non-insulin-dependent diabetes mellitus and compared with theoretical ones. Their weight functions against preceding plasma glucose level were analyzed assuming a stepwise plasma glucose change and compared with the theoretical prediction. RESULTS: The fasting plasma glucose level was acutely normalized after admission with a half-time of 6.3 +/- 2.4 days (mean +/- SD). The HbA1c level decreased linearly during the initial 2 months with a half-time of 34.6 +/- 10.1 days, followed by a gradual decrease thereafter. GA and FA levels decreased very rapidly during the initial 2-3 weeks with half-times of 17.1 +/- 2.8 and 12.2 +/- 4.8 days, respectively, followed by a gradual decrease thereafter. The time courses of HbA1c, GA, and FA agreed well with theoretically estimated decay curves. Experimental values of weight functions against the preceding plasma glucose level agreed well with the theoretical prediction. The weight functions for glycated proteins had maximum values on the days just before the measurement of glycated proteins and gradually decreased with an increasing time interval. The lengths of the periods over which the weight functions for HbA1c, GA, and FA extend back were estimated to be roughly 100, 40, and 30 days, respectively. CONCLUSIONS: The levels of HbA1c, GA, and FA do not reflect the simple mean but reflect the weighted mean of the preceding plasma glucose level over a considerably longer period than was previously speculated.

Analysis of early-phase insulin responses in nonobese subjects with mild glucose intolerance.

OBJECTIVE: To study the possible contribution of a B-cell defect in the development of glucose intolerance in nonobese subjects. RESEARCH DESIGN AND METHODS: There were 41 normal, nondiabetic subjects; 18 subjects with IGT; and 21 patients with NIDDM. All subjects were nonobese (BMI < 27 kg/m2). Insulin secretory responses to an OGTT, IVGTT, and GST were studied. RESULTS: Early-phase insulin responses to OGTT and IVGTT were decreased in subjects with IGT to levels comparable with those in NIDDM patients, whereas the response to GST was preserved in the subjects with IGT compared with NIDDM patients. The insulinogenic index of OGTT correlated well (r = 0.78) with early-phase insulin response to IVGTT, suggesting that the insulinogenic index in OGTT is related to the early-phase insulin response to IVGTT in nonobese subjects. CONCLUSIONS: Impaired early-phase insulin response to glucose was associated with mild glucose intolerance, suggesting the importance of impaired insulin secretion in the development of glucose intolerance in nonobese subjects.

Effective CpG DNA delivery using amphiphilic cycloamylose nanogels.

Unmethylated CpG oligodeoxynucleotides induce inflammatory immune responses through cytokine production and have attracted increasing attention as an immunostimulator. However, there remains a challenging issue of the use of 'native CpG DNA'. In the present study, we prepared cationic nanometer-sized gels (nanogels) consisting of cycloamylose modified with cholesterol and diethylaminoethane to form hydrophobic cross-linking points and to add positively charged groups, respectively. The cationic nanogels and native CpG DNA formed nanometer-sized complexes. Complexes of native CpG DNA with cationic nanogels delivered native CpG DNA to macrophage-like cells and induced cytokine production. In addition, complexes of negative control oligonucleotides with cationic nanogels did not induce cytokine production, and the induction of cytokines using complexes of phosphorothioate-modified CpG with cationic nanogels was lower than that of native CpG DNA. These results suggest that the complex of native CpG DNA with cationic nanogels is a promising strategy for nucleic acid adjuvants.

Maternal restraint stress during pregnancy in mice induces 11ß-HSD1-associated metabolic changes in the livers of the offspring.

In rats, maternal exposure to restraint stress during pregnancy can induce abnormalities in the cardiovascular and central nervous systems of the offspring. These effects are mediated by long-lasting hyperactivation of the hypothalamic-pituitary-adrenal axis. However, little is known about the potential effects of stress during pregnancy on metabolic systems. We examined the effect of restraint stress in pregnant mice on the liver function of their offspring. The offspring of stressed mothers showed significantly higher lipid accumulation in the liver after weaning than did the controls; this accumulation was associated with increased expression of lipid metabolism-related proteins such as alanine aminotransferase 2 diglyceride acyltransferase 1, peroxisome proliferator-activated receptor gamma and glucocorticoid receptor. Additionally, we observed increased levels of 11ß-hydroxysteroid dehydrogenase type 1, an intercellular mediator that converts glucocorticoid from the inactive to the active form, in the foetal and postnatal periods. These results indicate that restraint stress in pregnancy in mice induces metabolic abnormalities via 11ß-hydroxysteroid dehydrogenase type 1-related pathways in the foetal liver. It is therefore possible that exposure to stress in pregnant women may be a risk factor for metabolic syndromes (e.g. fatty liver) in children.

A pH induced two-dimensional crystal of membrane-bound Na+,K(+)-ATPase of dog kidney.

Two-dimensional crystals of membrane-bound Na+,K(+)-ATPase were formed in acidic media and their qualities were investigated by electron cryo-microscopy as well as by conventional electron microscopy. At pH 4.8 in sodium citrate buffer, the best crystallization condition, more than 80% of membranes formed crystals. The high ratio allowed high-resolution images to be taken by electron cryo-microscopy. Image processing revealed that they had unique lattice constants (a = 108.7 A, b = 66.2 A, gamma = 104.2 degrees) and had few defects in the crystalline arrays. The reconstituted Fourier map of the ice-embedded crystal showed that there are two high contrast parts in one unit cell.

Metabolism of intravenously administered maltose in renal tubules in humans.

To investigate how urinary excretion rates (UERs) of maltose and glucose are determined after intravenous maltose infusion, maltose and glucose solutions were infused at various rates and the relationships between UERs of maltose and glucose and their plasma concentrations were examined. Results showed the existence of a threshold plasma maltose concentration for the urinary excretions of maltose and glucose and the existence of a maximum rate of urinary glucose excretion after maltose infusion. Elevation of plasma glucose concentration by simultaneous glucose infusion increased urinary glucose excretion but did not increase urinary maltose excretion; the relationship between plasma total sugar concentration and urinary total sugar excretion was unchanged. Results suggest that maltose administered intravenously is hydrolyzed to glucose by maltase in renal tubules and reabsorbed as glucose competitively with glucose derived from plasma and that the maximum utilization of intravenously infused maltose is determined by the tubular glucose reabsorption capacity.

Continuous ambulatory radionuclide monitoring of left ventricular function: effect of body position during ergometer exercise.

UNLABELLED: We assessed the reliability of a continuous ambulatory radionuclide monitoring system (the VEST system, Capintec, Inc., Ramsey, NJ) for measurement of left ventricular performance during exercise in the upright and supine positions. METHODS: Sixteen healthy male volunteers (aged 32-46 yr; mean age 37 +/- 4 yr) were studied. All volunteers underwent ergometer exercise testing in both the upright and supine positions, and left ventricular performance was determined with the VEST system. RESULTS: The resting heart rate, systolic blood pressure, pressure rate product, relative end-diastolic volume, relative end-systolic volume and left ventricular ejection fraction (LVEF) all showed no differences between the upright and supine positions. At peak exercise, the heart rate, systolic blood pressure and pressure rate product showed no differences between the upright and supine positions. In the upright position at peak exercise the relative end-diastolic volume was increased (83% +/- 9% to 91% +/- 11%, p < 0.001); the relative end-systolic volume remained unchanged (34% +/- 3% to 33% +/- 15%), and LVEF was significantly increased from 58% +/- 6% to 66% +/- 11% (p < 0.01). In the supine position at peak exercise, the relative end-diastolic volume remained unchanged (85% +/- 5 to 83% +/- 7%), the relative end-systolic volume was increased (35% +/- 5% to 43% +/- 13%, p < 0.01), and LVEF was decreased from 58% +/- 5% to 48% +/- 17% (p < 0.01). These results indicated inferior data collection by the VEST system in the supine position. CONCLUSION: Since the detector of the VEST system may be too small, the data collection is impaired during exercise in the supine position by shifting the heart with deep respiration. The VEST system is very useful for determining left ventricular performance when applied in the sitting or upright position. However, in the supine position during exercise, the use of the VEST system should be avoided because it might indicate an artifactual deterioration of left ventricular performance.